Journal of Molecular and Cellular Cardiology
Volume 43, Issue 2 , Pages 168-176 , August 2007

Simvastatin inhibits TNFα-induced invasion of human cardiac myofibroblasts via both MMP-9-dependent and -independent mechanisms

  • Neil A. Turner

      Affiliations

    • Academic Unit of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Parvinder K. Aley

      Affiliations

    • Academic Unit of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Kersten T. Hall

      Affiliations

    • Academic Unit of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Philip Warburton

      Affiliations

    • Academic Unit of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Stacey Galloway

      Affiliations

    • Academic Unit of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Lynne Midgley

      Affiliations

    • Academic Unit of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS2 9JT, UK
    • ,
  • David J. O'Regan

      Affiliations

    • Department of Cardiac Surgery, The Yorkshire Heart Centre, Leeds General Infirmary, Leeds LS1 3EX, UK
    • ,
  • Ian C. Wood

      Affiliations

    • Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Stephen G. Ball

      Affiliations

    • Academic Unit of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS2 9JT, UK
    • ,
  • Karen E. Porter

      Affiliations

    • Academic Unit of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS2 9JT, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44 113 3434806; fax: +44 113 3434803.

Received 9 February 2007 ,Revised 4 April 2007 ,Accepted 11 May 2007.

References 

  1. Jugdutt BI. Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough?. Circulation. 2003;108:1395–1403
  2. Brown RD, Ambler SK, Mitchell MD, Long CS. The cardiac fibroblast: therapeutic target in myocardial remodeling and failure. Annu. Rev. Pharmacol. Toxicol. 2005;45:657–687
  3. Weber KT. Fibrosis in hypertensive heart disease: focus on cardiac fibroblasts. J. Hypertens. 2004;22:47–50
  4. Camelliti P, Borg TK, Kohl P. Structural and functional characterisation of cardiac fibroblasts. Cardiovasc. Res. 2005;65:40–51
  5. Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol. Rev. 1999;79:215–262
  6. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling—Concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J. Am. Coll. Cardiol. 2000;35:569–582
  7. Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the vesnarinone trial (VEST). Circulation. 2001;103:2055–2059
  8. Ferrari R, Bachetti T, Confortini R, Opasich C, Febo O, Corti A, et al. Tumor necrosis factor soluble receptors in patients with various degrees of congestive heart failure. Circulation. 1995;92:1479–1486
  9. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J. Am. Coll. Cardiol. 1996;27:1201–1206
  10. Bozkurt B, Kribbs SB, Clubb FJ, Michael LH, Didenko VV, Hornsby PJ, et al. Pathophysiologically relevant concentrations of tumor necrosis factor-a promote progressive left ventricular dysfunction and remodeling in rats. Circulation. 1998;97:1382–1391
  11. Bryant D, Becker L, Richardson J, Shelton J, Franco F, Peshock R, et al. Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha. Circulation. 1998;97:1375–1381
  12. Yokoyama T, Nakano M, Bednarczyk JL, McIntyre BW, Entman M, Mann DL. Tumor necrosis factor-α provokes a hypertrophic growth response in adult cardiac myocytes. Circulation. 1997;95:1247–1252
  13. Klein JB, Wang GW, Zhou Z, Buridi A, Kang YJ. Inhibition of tumor necrosis factor-alpha-dependent cardiomyocyte apoptosis by metallothionein. Cardiovasc. Toxicol. 2002;2:209–218
  14. Jacobs M, Staufenberger S, Gergs U, Meuter K, Brandstatter K, Hafner M, et al. Tumor necrosis factor-a at acute myocardial infarction in rats and effects on cardiac fibroblasts. J. Mol. Cell. Cardiol. 1999;31:1949–1959
  15. Porter KE, Turner NA, O'Regan DJ, Ball SG. Tumor necrosis factor a induces human atrial myofibroblast proliferation, invasion and MMP-9 secretion: inhibition by simvastatin. Cardiovasc. Res. 2004;64:507–515
  16. Doggrell SA. Statins in the 21st century: end of the simple story?. Expert Opin. Investig. Drugs. 2001;10:1755–1766
  17. Werner N, Nickenig G, Laufs U. Pleiotropic effects of HMG-CoA reductase inhibitors. Basic Res. Cardiol. 2002;97:105–116
  18. Bauersachs J, Galuppo P, Fraccarollo D, Christ M, Ertl G. Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme A reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction. Circulation. 2001;104:982–985
  19. Hayashidani S, Tsutsui H, Shiomi T, Suematsu N, Kinugawa S, Ide T, et al. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation. 2002;105:868–873
  20. Luo JD, Zhang WW, Zhang GP, Guan JX, Chen X. Simvastatin inhibits cardiac hypertrophy and angiotensin-converting enzyme activity in rats with aortic stenosis. Clin. Exp. Pharmacol. Physiol. 1999;26:903–908
  21. Nahrendorf M, Hu K, Hiller KH, Galuppo P, Fraccarollo D, Schweizer G, et al. Impact of hydroxymethylglutaryl coenzyme A reductase inhibition on left ventricular remodeling after myocardial infarction: an experimental serial cardiac magnetic resonance imaging study. J. Am. Coll. Cardiol. 2002;40:1695–1700
  22. Patel R, Nagueh SF, Tsybouleva N, Abdellatif M, Lutucuta S, Kopelen HA, et al. Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation. 2001;104:317–324
  23. Raina A, Pickering T, Shimbo D. Statin use in heart failure: a cause for concern?. Am. Heart J. 2006;152:39–49
  24. van der Harst P, Voors AA, van Gilst WH, Bohm M, van Veldhuisen DJ. Statins in the treatment of chronic heart failure: biological and clinical considerations. Cardiovasc. Res. 2006;71:443–454
  25. Khush KK, Waters DD. Effects of statin therapy on the development and progression of heart failure: mechanisms and clinical trials. J. Card. Fail. 2006;12:664–674
  26. Turner NA, Porter KE, Smith WH, White HL, Ball SG, Balmforth AJ. Chronic β2-adrenergic receptor stimulation increases proliferation of human cardiac fibroblasts via an autocrine mechanism. Cardiovasc. Res. 2003;57:784–792
  27. Porter KE, Turner NA, O'Regan DJ, Balmforth AJ, Ball SG. Simvastatin reduces human atrial myofibroblast proliferation independently of cholesterol lowering via inhibition of RhoA. Cardiovasc. Res. 2004;61:745–755
  28. Turner NA, Hall KT, Ball SG, Porter KE. Selective gene silencing of either MMP-2 or MMP-9 inhibits invasion of human saphenous vein smooth muscle cells. Atherosclerosis. 2007;193:36–43
  29. Porter KE, Naik J, Turner NA, Dickinson T, Thompson MM, London NJ. Simvastatin inhibits human saphenous vein neointima formation via inhibition of smooth muscle cell proliferation and migration. J. Vasc. Surg. 2002;36:150–157
  30. Turner NA, Ball SG, Balmforth AJ. The mechanism of angiotensin II-induced extracellular signal-regulated kinase-1/2 activation is independent of angiotensin AT1A receptor internalisation. Cell. Signal. 2001;13:269–277
  31. Melchert RB, Liu H, Granberry MC, Kennedy RH. Lovastatin inhibits phenylephrine-induced ERK activation and growth of cardiac myocytes. Cardiovasc. Toxicol. 2001;1:237–252
  32. Ortego M, Bustos C, Hernández-Presa MA, Tuñón J, Díaz C, Hernández G, et al. Atorvastatin reduces NF-κB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. Atherosclerosis. 1999;147:253–261
  33. Cho A, Reidy MA. Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ. Res. 2002;91:845–851
  34. Galis ZS, Johnson C, Godin D, Magid R, Shipley JM, Senior RM, et al. Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ. Res. 2002;91:852–859
  35. Loirand G, Guerin P, Pacaud P. Rho kinases in cardiovascular physiology and pathophysiology. Circ. Res. 2006;98:322–334
  36. Olivo C, Vanni C, Mancini P, Silengo L, Torrisi MR, Tarone G, et al. Distinct involvement of cdc42 and RhoA GTPases in actin organization and cell shape in untransformed and Dbl oncogene transformed NIH3T3 cells. Oncogene. 2000;19:1428–1436
  37. Yarrow JC, Totsukawa G, Charras GT, Mitchison TJ. Screening for cell migration inhibitors via automated microscopy reveals a Rho-kinase inhibitor. Chem. Biol. 2005;12:385–395
  38. Bellosta S, Via D, Canavesi M, Pfister P, Fumagalli R, Paoletti R, et al. HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages. Arterioscler. Thromb. Vasc. Biol. 1998;18:1671–1678
  39. Luan Z, Chase AJ, Newby AC. Statins inhibit secretion of metalloproteinases-1, -2, -3, and -9 from vascular smooth muscle cells and macrophages. Arterioscler. Thromb. Vasc. Biol. 2003;23:769–775
  40. Turner NA, O'Regan DJ, Ball SG, Porter KE. Simvastatin inhibits MMP-9 secretion from human saphenous vein smooth muscle cells by inhibiting the RhoA/ROCK pathway and reducing MMP-9 mRNA levels. FASEB J. 2005;19:804–806
  41. Rahat MA, Marom B, Bitterman H, Weiss-Cerem L, Kinarty A, Lahat N. Hypoxia reduces the output of matrix metalloproteinase-9 (MMP-9) in monocytes by inhibiting its secretion and elevating membranal association. J. Leukoc. Biol. 2006;79:706–718
  42. Ma Z, Shah RC, Chang MJ, Benveniste EN. Coordination of cell signaling, chromatin remodeling, histone modifications, and regulator recruitment in human matrix metalloproteinase 9 gene transcription. Mol. Cell. Biol. 2004;24:5496–5509
  43. Sehgal I, Thompson TC. Novel regulation of type IV collagenase (matrix metalloproteinase-9 and -2) activities by transforming growth factor-beta1 in human prostate cancer cell lines. Mol. Biol. Cell. 1999;10:407–416
  44. Akool E-S, Kleinert H, Hamada FMA, Abdelwahab MH, Förstermann U, Pfeilschifter J, et al. Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR. Mol. Cell. Biol. 2003;23:4901–4916
  45. Jiang Y, Muschel RJ. Regulation of matrix metalloproteinase-9 (MMP-9) by translational efficiency in murine prostate carcinoma cells. Cancer Res. 2002;62:1910–1914
  46. Fahling M, Steege A, Perlewitz A, Nafz B, Mrowka R, Persson PB. Role of nucleolin in posttranscriptional control of MMP-9 expression. Biochim. Biophys. Acta. 2005;1731:32–40

PII: S0022-2828(07)01045-0

doi: 10.1016/j.yjmcc.2007.05.006

Journal of Molecular and Cellular Cardiology
Volume 43, Issue 2 , Pages 168-176 , August 2007

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